We study mechanisms of immunesurveillance. The immune system detects and eliminates microbial pathogens and cancer cells. Regrettably, the immune system also rejects transplanted tissues and often self-tissues as well. We have identified several antigen genes that uniquely define cancer cells, microbial pathogens, and transplanted tissues as targets for the immune system. We study the molecular mechanisms that generate these antigenic structures and determine their immunogenicity.

The T lymphocytes recognize peptides bound to MHC molecules on the surface of antigen presenting cells (APC). Because the peptides are derived from intracellular proteins the display of these peptide/MHC complexes on the APC surface allows T cells to detect antigens that are sequestered intracellularly and thus, inaccessible to soluble antibody molecules. The antigen processing pathway continuously degrades thousands of intracellular proteins into peptide fragments that are transported to the APC surface by the MHC molecules. When the MHC molecules are found to contain unique peptides derived from viruses, bacteria or mutated genes, the T cells can eliminate the cells bearing these peptide/MHC complexes. The repertoire of peptide/MHC complexes thus defines the immunological identity of cells as perceived by the T cell receptors. The identity and source of these unique peptide/MHC and the antigen processing mechanisms that generate them are poorly understood.